Does autosomal dominant polycystic kidney disease increase the risk of aortic aneurysm or dissection: a point of view based on a systematic review and meta-analysis.

Autosomal Dominant Polycystic Kidney Disease (ADPKD) has several renal and extra-renal manifestations. Studies have reported a higher incidence of aortic aneurysms (AAs)/aortic dissections (ADs) in these patients, and we believe ADPKD should be considered as a risk factor for AA/AD. In order to support our opinion we conducted a systematic review and meta-analysis analyzing the risk of AA/AD in ADPKD patients.We searched MEDLINE, CENTRAL, PsycInfo, Web of Science Core Collection and OpenGrey for observational studies reporting frequency estimates of AA/AD in ADPKD patients compared with controls. We analyzed the odds ratio (OR) of the existence of an AA/AD in patients with ADPKD compared to controls. We also analyzed the odds of having an AA in patients with ADPKD compared to controls, the odds of having an AD in patients with ADPKD compared to controls, differences among subtypes of AA or AD, differences according to age, gender and different study designs.Seven observational studies were included. ADPKD was associated with a higher risk of AA or AD as compared with a population without the disease (OR 4.33; 95% CI 2.69; 6.97, p < 0.001); higher risk of AA (OR 4.18; 95% CI 2.36; 7.40, p < 0.001) and higher risk of AD (OR 9.08; 95% CI 3.11; 26.55, p < 0.001).Our point of view, suggesting the inclusion of aortic aneurysms and aortic dissection in the potential complications of ADPKD, was supported by our systematic review and meta-analysis showing that ADPKD was associated with a significant risk of having/developing an AA/AD. However, the risk of bias of included studies was considered high and these results should be interpreted cautiously. This association should be considered in clinical practice, although further studies are needed to consolidate these findings.

Gla-Rich Protein, Magnesium and Phosphate Associate with Mitral and Aortic Valves Calcification in Diabetic Patients with Moderate CKD.

Accelerated and premature cardiovascular calcification is a hallmark of chronic kidney disease (CKD) patients. Valvular calcification (VC) is a critical indicator of cardiovascular disease and all-cause mortality in this population, lacking validated biomarkers for early diagnosis. Gla-rich protein (GRP) is a cardiovascular calcification inhibitor recently associated with vascular calcification, pulse pressure, mineral metabolism markers and kidney function. Here, we examined the association between GRP serum levels and mitral and aortic valves calcification in a cohort of 80 diabetic patients with CKD stages 2-4. Mitral and aortic valves calcification were detected in 36.2% and 34.4% of the patients and associated with lower GRP levels, even after adjustments for age and gender. In this pilot study, univariate, multivariate and Poisson regression analysis, show that low levels of GRP and magnesium (Mg), and high levels of phosphate (P) are associated with mitral and aortic valves calcification. Receiver operating characteristic (ROC) curves showed that the area under the curve (AUC) values of GRP for mitral (0.762) and aortic (0.802) valves calcification were higher than those of Mg and P. These results suggest that low levels of GRP and Mg, and high levels of P, are independent and cumulative risk factors for VC in this population; the GRP diagnostic value might be potentially useful in cardiovascular risk assessment.

Incidence, prevalence and crude survival of patients starting dialysis in Portugal (2010-16): analysis of the National Health System individual registry.

BACKGROUND: The Portuguese Society of Nephrology (PSN) reported that Portugal has one of the highest incidences of dialysis in Europe. However, this claim was based on aggregated data supplied by dialysis providers, hampering comparisons between countries. In 2009, an individual registry of patients starting dialysis was set up by the Portuguese Ministry of Health. We analysed individual data of patients starting dialysis from January 2010 until December 2016. METHODS: Demography, starting treatment day, modality, regional distribution and outcomes, such as death, recovery of renal function, transfer to renal transplantation, peritoneal dialysis or conservative management, were extracted. Incidence, prevalence and survival analysis were calculated and compared with the PSN registry. RESULTS: Out of 19 190 registrations, 16 775 were incident patients (61.8% men). Yearly incidence of renal replacement therapy was 250, 248, 229, 239, 230, 231 and 244 per million population (p.m.p.) for 2010 to 2016, compared with 235, 224, 218, 230, 234, 225 and 239 p.m.p. reported by the PSN registry. On the other hand, prevalence increased from 998 p.m.p. in 2010 to 1286 p.m.p. in 2016, compared with 1010 p.m.p. in 2010 increasing to 1203 p.m.p. in 2016 from the PSN registry. The regions of Alentejo (122.9 p.m.p.) and the the Centre (160.8 p.m.p.) had the lowest regional incidence, while Lisbon had the highest (386 p.m.p. in 2016). Unadjusted survival analysis revealed that 93.5% of the patients were alive on the 91st day, whereas 85.2 and 78.3% were alive at 1 and 2 years, respectively. Crude survival at 7 years was 40%. CONCLUSIONS: For the first time, an individual registry of patients starting dialysis in Portugal was subject to analysis and added new information about long-term survival and regional differences in the incidence and prevalence of renal replacement therapy. We were able to confirm that Portugal has one of the world's highest incidences and prevalences of dialysis. We also demonstrate, for the first time, a striking regional difference in the incidence of dialysis and an excellent early and long-term survival of patients on dialysis. These results compare well with other European countries in terms of the dialysis efficiency.

Gla-Rich Protein (GRP) as an Early and Novel Marker of Vascular Calcification and Kidney Dysfunction in Diabetic Patients with CKD: A Pilot Cross-Sectional Study.

Vascular calcification (VC) is one of the strongest predictors of cardiovascular risk in chronic kidney disease (CKD) patients. New diagnostic/prognostic tools are required for early detection of VC allowing interventional strategies. Gla-rich protein (GRP) is a cardiovascular calcification inhibitor, whose clinical utility is here highlighted. The present study explores, for the first time, correlations between levels of GRP in serum with CKD developmental stage, mineral metabolism markers, VC and pulse pressure (PP), in a cohort of 80 diabetic patients with mild to moderate CKD (stages 2-4). Spearman's correlation analysis revealed a positive association of GRP serum levels with estimated glomerular filtration rate (eGFR) and α-Klotho, while a negative correlation with phosphate (P), fibroblast growth factor 23 (FGF-23), vascular calcification score (VCS), PP, calcium (x) phosphate (CaxP) and interleukin 6 (IL-6). Serum GRP levels were found to progressively decrease from stage 2 to stage 4 CKD. Multivariate analysis identified low levels of eGFR and GRP, and high levels of FGF-23 associated with both the VCS and PP. These results indicate an association between GRP, renal dysfunction and CKD-mineral and bone disorder. The relationship between low levels of GRP and vascular calcifications suggests a future, potential utility for GRP as an early marker of vascular damage in CKD.

Evidence of a third ADPKD locus is not supported by re-analysis of designated PKD3 families.

Mutations to PKD1 and PKD2 are associated with autosomal dominant polycystic kidney disease (ADPKD). The absence of apparent PKD1/PKD2 linkage in five published European or North American families with ADPKD suggested a third locus, designated PKD3. Here we re-evaluated these families by updating clinical information, re-sampling where possible, and mutation screening for PKD1/PKD2. In the French-Canadian family, we identified PKD1: p.D3782_V3783insD, with misdiagnoses in two individuals and sample contamination explaining the lack of linkage. In the Portuguese family, PKD1: p.G3818A segregated with the disease in 10 individuals in three generations with likely misdiagnosis in one individual, sample contamination, and use of distant microsatellite markers explaining the linkage discrepancy. The mutation PKD2: c.213delC was found in the Bulgarian family, with linkage failure attributed to false positive diagnoses in two individuals. An affected son, but not the mother, in the Italian family had the nonsense mutation PKD1: p.R4228X, which appeared de novo in the son, with simple cysts probably explaining the mother's phenotype. No likely mutation was found in the Spanish family, but the phenotype was atypical with kidney atrophy in one case. Thus, re-analysis does not support the existence of a PKD3 in ADPKD. False positive diagnoses by ultrasound in all resolved families shows the value of mutation screening, but not linkage, to understand families with discrepant data.

Evaluation of an instrument for screening patients at risk for chronic kidney disease: testing SCORED (Screening for Occult Renal Disease) in a Portuguese population.

Prevalence of chronic kidney disease (CKD) is increasing and CKD has a long asymptomatic phase suitable for screening. SCORED (Screening for Occult Renal Disease) is a prescreening test which has compared favorably with KEEP. We report the results of SCORED testing in subjects attending a World Kidney Day event. After SCORED, subjects were tested for creatinine, urinary albumin and creatinine, and renal ultrasound. Eighty-eight subjects participated (32 men; mean age 59.7 ± 14.8 years; 58% hypertensive and 15.9% diabetics) of which 60 had a high score for kidney disease. Thirty-eight of 47 (80.8%) subjects that were further evaluated had a high-risk score. All subjects with CKD had a high score (100% sensitivity). SCORED showed low specificity (24.3%), but a high negative predictive value (100%). Including albuminuria in the definition of CKD increased the positive predictive value to 43.6%. In conclusion, SCORED is good for prescreening subjects for CKD in a European population as it captures all patients with CKD. Moreover, in subjects with low risk, the probability of CKD is low. SCORED is useful in alerting the general population and the medical community about the risk factors of CKD.

Ascites complicating unilateral nephrectomy and peritoneal dialysis catheter implantation in a patient with massive polycystic kidney and liver disease.

Peritoneal dialysis (PD) is a well-established therapeutic option for patients with polycystic kidney disease. However, in patients with massive polycystic kidney and liver disease, subclinical hepatic venous outflow obstruction may elicit the appearance of ascites after implantation of a peritoneal catheter. The case of a patient who developed ascites after implantation of a PD catheter and further lowering of abdominal pressure after unilateral nephrectomy is discussed.

IgA nephropathy in a patient presenting with scleritis.

Scleritis is a very uncommon manifestation in patients with IgA nephropathy. Here, we report the case of a patient presenting with diffuse anterior scleritis in which the laboratory disclosed microscopic haematuria and nephrotic range proteinuria. Renal function was normal. Serology for lupus, vasculitis and cryoglobulinaemia was negative. Rheumatoid factor was negative, and serum C3 and serum C4 were on the normal range. Serology for human immunodeficiency virus types 1 and 2, hepatitis B, hepatitis C, syphilis, and Lyme disease was also negative. A renal biopsy was performed and revealed IgA nephropathy. Oral steroids were then started, and 6 months later, the patient was asymptomatic. Scleritis did not recur, and ophthalmologic examination was normal; however, proteinuria was still in non-nephrotic range. Renal function still remains normal.

Bone mineral density, vascular calcifications, and arterial stiffness in peritoneal dialysis patients.

The objective of this study was to evaluate the correlation of bone mineral density (BMD), evaluated by DXA, with vascular calcifications, arterial stiffness, and vascular disease in patients on peritoneal dialysis. Vascular calcifications were evaluated by vascular calcification score on plain x ray, and arterial stiffness was measured by pulse wave velocity using the Complior device (Artech Medical, Pantin, France). Adjusting for multiple factors, lower BMD at the femoral neck, but not at the lumbar spine, was associated with higher pulse wave velocity (p = 0.037), higher vascular calcification score (p = 0.013), and peripheral artery disease (p = 0.006). These data reinforce the hypothesis of the existence of a link between bone disease and cardiovascular disease in dialysis patients.

Diastolic function in several stages of chronic kidney disease in patients with autosomal dominant polycystic kidney disease: a tissue Doppler imaging study.

BACKGROUND: This study evaluates the prevalence of diastolic dysfunction (DD) in several stages of chronic kidney disease (CKD) in patients with autosomal dominant polycystic kidney disease (ADPKD). METHODS: 107 ADPKD patients performed echocardiographic and Doppler studies and a tissue Doppler imaging (TDI) study. Patients were divided in three groups: group 1, 57 patients with CKD stage I, group 2, 37 patients in stages II and III, and group 3, 13 patients with CKD stages IV and V (not on dialysis). RESULTS: In transmitral Doppler, 1 patient in group 1 compared to 5 in group 2, and 4 in group 3 exhibited DD (p < 0.005); moreover, E/A ratio decreases progressively from group 1 to 3 (p < 0.0001). In TDI, DD was observed in 8 patients in group 1, 17 in group 2, and 8 in group 3 had DD (p < 0.001). Em velocity, the best TDI parameter for DD, correlated with age, renal function and blood pressure. When adjusted for age, increased left ventricular mass index and decreased renal function were independent risk factors of DD. CONCLUSIONS: DD occurred progressively as renal function deteriorates in patients with ADPKD and this effect is independently related to age and blood pressure.

Ambulatory blood pressure measurement in young normotensive patients with autosomal dominant polycystic kidney disease.

INTRODUCTION: Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic disorder causing chronic kidney disease in adults. Hypertension occurs early and frequently precedes the development of renal failure. It has been shown that clinically normotensive young adults with ADPKD exhibit increased left ventricular mass and left ventricular mass index (LVMI), which contributes to the increased cardiovascular risk in these patients. We set out to investigate whether normotensive patients have a prehypertensive state that could account for their increased LVMI. METHODS: Patients with ADPKD followed as outpatients were selected if they were aged between 21-30 years, were normotensive (office and sporadic blood pressure < 140/90 without medication), and had normal renal function (GFR > 90 ml/min). Normotensive controls aged between 21-30 years were selected, all with normal renal ultrasound, serum creatinine, dipstick analysis and microalbuminuria /creatinine ratio. Patients and controls underwent 24-hour ambulatory blood pressure measurement (ABPM) according to the local protocol. RESULTS: Systolic (124.7 +/- 7.6 vs. 115.2 +/- 6.9; p < 0.0001), diastolic (77.3 +/- 6.3 vs. 70.5 +/- 3.9; p < 0.0001) and mean (92.7 +/- 8.5 vs. 85.7 +/- < 0.001) 24-hour blood pressure was significantly higher in patients with ADPKD compared to controls. Statistically significant differences were also found when daytime and night-time periods were analyzed separately. Hypertension on ABPM was diagnosed in 6 patients but differences in the ABPM profile persisted even when these patients were excluded from the analysis. CONCLUSION: In young adults with ADPKD there is a prehypertensive state that can be detected using ABPM.

Fungal peritonitis in peritoneal dialysis patients: Is previous antibiotic therapy an essential condition?

The aim of this study was to analyse the clinical and microbiological features of fungal peritonitis, in chronic peritoneal dialysis patients, focusing on non-traditional risk factors for this feared complication. From 2001 to 2004, five episodes of fungal peritonitis were diagnosed in five different patients, accounting for 4.5% of all peritonitis cases seen during this period. Candida spp. were the most frequent isolates. In all cases, peritoneal dialysis catheter removal and switching to haemodialysis were necessary. In these five cases of fungal peritonitis only one was preceded by antibiotic use, within the previous 3 months, the classical risk factor for fungal peritonitis. Identifying predisposing factors usually not taken into account, may lead to an early diagnosis and to a better understanding of fungal peritonitis pathogenesis.

Hypertension in autosomal dominant polycystic kidney disease: observational study in 207 patients with a mean follow-up of 107 months.

INTRODUCTION AND OBJECTIVES: Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common hereditary diseases in adults. ADPKD is a frequent cause of 4 secondary hypertension and, conversely, hypertension is a common manifestation of ADPKD and, more importantly, one of the few that are treatable. Given the autosomal dominant nature of the disease and the fact that it is easy to diagnose with a renal scan, ADPKD patients can be diagnosed early at a pre-symptomatic stage, and hypertension can be detected and treated. The main purpose of this article is to report our experience in the long-term follow-up of patients with ADPKD, with particular emphasis on hypertension. METHODS: A retrospective analysis was made of 532 patients observed in our outpatient clinic due to renal cysts over the last 17 years, of whom 383 were diagnosed with ADPKD according to Ravine's criteria. Patients were followed-up as outpatients on a yearly basis, or more frequently if necessary. Data on demography and clinical findings were analyzed with particular emphasis on blood pressure control, number and type of antihypertensive drugs, and left ventricular mass index (LVMI). RESULTS: At the beginning of follow-up 56% of the patients, including 30.7% of the young adults aged 20 to 34 years, were hypertensive. Focusing on 207 patients observed in 2006, with a mean follow-up of 107 +/- 66 months, a significant decrease in systolic and diastolic blood pressure was observed between the first and last observations. Of a subgroup of 115 patients who were normotensive at the initial observation, 50% became hypertensive by the age of 40. During follow-up, only eleven had a cardiovascular event such as angina, myocardial infarction, stroke or peripheral artery disease (rate 0.006 events/patient-year). LVMI correlated with age, renal function and systolic and diastolic blood pressure, but only age was an independent risk factor for increased left ventricular mass. CONCLUSION: Hypertension is a common complication in ADPKD patients. Early diagnosis and follow-up at a pre-symptomatic stage of the disease are important since this enables early initiation of antihypertensive therapy, which could reduce the rate of cardiovascular events in this population.